Psyc 689 Clin Psychopharmacology

Neurophysiology

Neuron Components

Soma (Cell Body) Neurites (any process

that extends from cell body) Axon Dendrites

Terminal Buttons

Pre

Post

Classification of Neurons Number of axon processes (unipolar,

bipolar, multipolar) Number of dendritic processes Function

Sensory, motor, interneurons Neurotransmitter (NT) used by neuron

(e.g. cholinergic neurons) Effects of NT (excitatory vs. inhibitory)

Bipolar - Unipolar Neurons

Neuron Cell Structure Cell Specializations: Support, contraction, conduction,

secretion Nerve cells are specialized for communication

(nerves conduct ELECTROCHEMICAL signals) Cell components

Membrane: bilipid layer contains ion channels and receptors

Cytoplasm Mitochondria (energy for cell) Nucleus (contains DNA, guides protein synthesis) Microfilaments and tubules: transport functions Transporters (membrane, vesicular)

Measuring Nerve Cell Resting Membrane Potential

Giant squid axon is placed in seawater in recording chamber

Glass microelectrode is inserted into axon Voltage measures -70

mV inside with respect to outside

-70 mV

Chamber

Axon

Voltmeter

Microelectrode

Resting Membrane Potential RMP is a balance point between

Concentration gradients Electrical gradients

RMP reflects a selective permeability to K+ At rest, some K+ can leave cell, causing the

exterior of the nerve cell membrane to be slightly positive relative to the inside of the axon

RMP can change briefly (local potentials) Depolarizing Hyperpolarizing

Ion Channels

Channels allow for entry/efflux of ions Channel opening/closing mechanisms:

Ligand-gated Second messenger-gated Voltage-gated Stretch-gated

Impact of ion channel will depend on charge/direction of ion flow

[Ion] Relative to Membrane

ION: [OUT] [IN]======================================

NA+ 120 10

K+ 3 140

CL- 120 3

AN- NIL 100========================================

Local Potentials

Local disturbances of membrane potential are carried along the membrane : Local potentials

degrade with time and distance

Local potentials can summate to produce an action potential (AP)

-70 mV

-60 mV

-70 mV-65 mV

Decremental Conduction

-70 mV-55 mV

Pre-synaptic Neuron Post-synaptic Neuron

Axon

Action Potentials are generatedin the initial segment (axon hillock)

when the RMP rises above threshold.

The initial segment has a high densityof voltage-gated sodium channels.

PSP’s

PSP’s

PSP’s

The Action Potential (AP) An AP is a stereotyped change in

membrane potential If RMP moves past threshold,

membrane potential quickly moves to +40 mV and then returns to resting level (-70 mV)

Ionic basis of the AP: NA+ in: upswing of spike

Diffusion, electrostatic pressure K+ out: downswing of spike

Source: Fig 4.14 from Kolb, Whishaw (2001)Brain and Behavior.

Action Potential Properties

The action potential: Is an “all or none” event: RMP either passes

threshold or doesn’t Is propagated down the axon membrane

Notion of “successive patches” of membrane Has a fixed amplitude: AP’s don’t signal

information via a change in height APs vary in frequency to signal information

Has a conduction velocity (10-100 meters/sec) Has a refractory period in which stimulation

will not produce an AP (limits the firing rate)

Membrane Refractory Periods

Absolute: ~1 msec (during impulse) Relative: following repolarization RP’s limit the firing rate of nerve cells

1 msec RP would = 1000 pulses per second

Absolute RP explains why AP typically cannot travel in 2 directions simultaneously

Saltatory Conduction AP’s are propagated down axon

AP depolarizes each successive patch of membrane

Slows down transmission in nonmyelinated axons

Myelinated axons: AP jumps from node to node: only depolarizes membrane at node

Saltatory conduction speeds up velocity and allows for smaller diameter axons

Saltatory Conduction

Inter-Neuron Signaling

Messages from one nerve cell are passed onto another nerve cell: Direct electrical

contact Chemical signals

between neurons? Nerve cells release

chemicals: The Loewi study

Synapses The “synapse” is the physical gap between pre-

and post-synaptic membranes (~20-40 nMeters) Presynaptic membrane is typically an axon The axon terminal contains

Mitochondria that provide energy for axon functions Vesicles (round objects) - contain neurotransmitter molecules Cisternae (part of the Golgi apparatus): recycle vesicles

Postsynaptic membrane can be A dendrite (axodendritic synapse) A cell body (axosomatic synapse) Another axon (axoaxonic synapse)

Postsynaptic thickening lies under the axon terminal and contains receptors for transmitters

Types of Synapses

• Electrical • Chemical

•Found in: escape reflex neurons (e.g. goldfish)•Epithelial cells (gut)•Cardiac muscle cells (heart)

•Found in: Almost all mammalian neurons

Figure 5.1a, Bear, 2001Figure 5.10, Bear, 2001

Figure 4-18b, Sherwood, 2001

Property Electrical Synapse

Distance between

Membranes

3.5 nm

Cytoplasmic continuity?

Yes

Structural Unit(s)

Gap-junction channel

Transmitter Ionic current

Transmission Delay

No

Transmission Direction

Can be bi-directional

Chemical Synapse

20-40 nm

No

Many (vesicles, docking/fusion proteins, and postsynaptic

receptors)

Chemical transmitter (can be modified using drugs)

Yes (usually 1-5 msec)

Unidirectional

Receptor’s View of the Presynaptic Terminal

Figure 5.11, Bear, 2001

Before stimulation (and 10msec after stimulation)

1msec after stimulation

Neurotransmitter Release Vesicles lie “docked” near the presynaptic

membrane The arrival of an action potential at the axon

terminal opens voltage-dependent CA++ channels CA++ ions flow into the axon CA++ ions change the structure of the proteins that bind

the vesicles to the presynaptic membrane A fusion pore is opened, which results in the merging of

the vesicular and presynaptic membranes The vesicles release their contents into the synapse

Released transmitter then diffuses across cleft to interact with postsynaptic membrane receptors

Postsynaptic Receptors Molecules of neurotransmitter (NT) bind to

receptors located on the postsynaptic membrane Receptor activation opens postsynaptic ion channels Ions flow through the membrane, producing either

depolarization or hyperpolarization The resulting postsynaptic potential (PSP) depends on

which ion channel(s) open Postsynaptic receptors alter ion channels

Directly (ionotropic receptors) Indirectly, using second messenger systems

that require energy (metabotropic receptors)

Ligand-gated Ion Channel Receptors

Note that Cl- is responsible for hyperpolarization Note that Na+ is responsible for depolarization These receptors are made up of 5 subunits

each with 4 TM segments

G Protein-Coupled Receptors

Postsynaptic Potentials

PSPs are either excitatory (EPSP) or inhibitory (IPSP) Opening NA+ ion channels results in an EPSP Opening K+ ion channels results in an IPSP Opening Cl- ion channels results in an IPSP

Depends on value of membrane potential

PSPs sweep along the membrane Degrade with distance and time

Length and time constants

EPSP Generation (NA+ Influx)

The equil point forNA is about +40 mV

IPSP Generation (Cl- Influx)

The equil point forCl is about –60 mV

Termination of Postsynaptic Potentials

NT binding to a postsynaptic receptor results in a temporary PSP

Termination of PSPs is accomplished via Reuptake: the NT molecule is transported

back into the cytoplasm of the presynaptic membrane

The NT molecule can be reused Vesicular transporters can move NT into vesicles

Enzymatic deactivation: an enzyme destroys the NT molecule

Diffusion away from the receptor sites

Membrane Transporters Two types of

transporters: Membrane

transporters Move NT into cytoplasm Reuptake blockade will

increase synaptic [NT] Vesicular transporters

Move NT into vesicles

Synaptic Integration PSPs sweep along the dendritic membrane

The amplitude of a PSP varies with time and distance

Length constant: larger values mean greater amplitude over a fixed distance

Neural integration involves the algebraic summation of PSPs A predominance of EPSPs at the axon hillock can

result in an action potential If the summated PSPs do not drive the axon

membrane past threshold, no action potential will occur

EPSP Summation

SpatialSummation

TemporalSummation

Property Action Pot EPSP IPSP

Direction More +Depolarization

More +Hypopolarization

More -Hyperpolarization

Magnitude All or None -70 to threshold -70 to -96 -70 to +30

ConductionProperties Decremental Decremental Decremental

Duration 2-3 msec 15-20 msec 15-20 msec

Non-